Exam 1: Virology I Flashcards
Virus
Nucleic acid surrounded by a protein coat = nucleic capsid
Not living organisms but either have DNA or RNA, not both
Obligate intracellularparasites: cannot produce energy, no metabolism, no reproduction, etc.
Naked viruses or have a nuclear envelop (membrane) from the host
Viruses are unable to make energy, synthesize their own proteins, or replicate their genome independently of host cells
Viral Properties vs. Cell
Nucleic Acid: either DNA or RNA (not both)
Proteins: few (cells have many)
Lipoprotein Membrane: envelope present in some (cells all have membranes)
Ribosomes: absent
Mitochondria: absent
Energy/ATP production: None
Enzymes: none or few
Non Enveloped
dsDNA: papovaviridae, adencoviridae, adenovirus
dsRNA: reoviridae
ssRNA: picornaviridae and calicivirus
ssDNA: parvoviridae
Enveloped
dsDNA: poxviridae, herpesviridae, hepadnaviridiae
ssRNA: paramyxoviridae, orthomyxoviridae, rhabdoviridae, retroviridae, arenaviridae, coronaviridae, bunyaviridae, togavirdae (Rubella), and flaviviridae
Viral Shape, Size, and Envelope
Size of viruses can vary- bacteriophage MS2 size and can reach a size as big as Chlamydia
Compared to E.coli, viruses are small
Piconavirus: have RNA as genome and very tightly packed because small
Largest virus (Poxvirus) is as large as Chlamydia but much smaller than E. coli
Viral Structure: Naked and Enveloped
We differentiate enveloped vs. non enveloped
Bacteriophage: capsid with nucleic acid to be injected into the host bacteria; naked/no envelope; the only thing that enters the cell is the DNA/RNA
Human viruses: they enter their capsid protein and nucleic acid; removal of the protein capsid and then freeing of the nucleic acid for reproduction happen within the host
Glycoprotein membrane: allows the glycoproteins to act as receptors that enable the virus to bind/attach to the host cell when it is going to infect it
Classification of Viruses
Several systems for classification of viruses have been used in the past
Most of these have been based on: viral disease, symptoms, and mode of transmission
In 1966, the International Committee on the nomenclature of Viruses was formed. Criteria for classification: mucleic acid type, composition, and size, virus morphology, serological cross-reactivity of group antigens
Morphology, physicochemical properties, genome properties, virus protein properties, biologic properties, antigenic properties
Morphology of Viruses
Size
Shape
Symmetry
Presence or absence of peplomers, which are virus-encoded glycoproteins inserted onto virus envelope
Presence or absence of envelope (membrane)
Physiochemical Properties
Molecular mass Density pH stability Thermal stability Susceptibility to physical and chemical agents such as ether and detergents
Genome Properties
Nucleic acid: DNA or RNA; ss or ds; linear or circular (linear is most common)
Size and type of genome
Sense: positive or negative
Segments (e.g., influenza)
Special features: 5’-terminal cap, 5’-terminal covalently linked protein, 3’-terminal poly[A] trail
Retroviruses contain RT (reverse transcriptase)
Capping enzymes to modify viral mRNA at their 5’ end by adding 7- methylguanosine
Polyadenylation of the 3’ end of viral mRNA
Virally coded enzymes: protein kinases, phosphatases, endonucleases, and RNAses
Virus Protein Properties
Number Size Functional activities Amino acid sequence Modifications (glycosylation) Functional activities (transcriptase, RT, neuraminidase, fusion activities)
Biologic Properties
Natural host range: mode of transmission, vector relationship, pathogenicity, tissue tropism
Antigenic properties: serologic relationship with the host
Universal System of Virus Taxonomy
Families (morphology, genome structure, and strategies of replication).
Suffix “-viridae”
Genera (subdivision): based on physicochemical, serology, cytopathology, or epidemiology.
Viral Architecture
Three groups: Icosahedral symmetry: has 20 faces (e.g., adenoviruses) Helical symmetry (e.g., orthomyxoviruses) Complex structure (e.g., poxviruses): has two membranes, one on the outside and one on the core with nucleic acid (DNA); outside one has the lateral bodies
Capsid vs. Nucleocapsid vs. Envelope
Capsid: protein shell, or coat. Encloses the nucleic acid genome
Nucleocapsid: protein-nucleic acid complex
Enveloped virus in addition to capsid, there is a membrane that surrounds the whole structure; membrane is biological composed of phospholipids with spikes
Outer Shell/Envelope:
1. Protects genome
2. Aids in the process of entry into the cell
3. Packages enzymes essential for the early
steps of the infectious process
Icosahedral Capsid Symmetry: No Envelope
Papillomaviruses/Papovavirus, Parvovirus, Adenovirus
Two key components:
1. Central core (the genome)
2. Outer shell of protein known as the capsid (made of proteins)
The capsid of each virus is an aggregation of morphologic units known as capsomeres
The core and capsid are known as the nucleocapsid
Icosahedral Capsid Symmetry with Envelope
Rubellavirus/Togavirus, Herpes, and HepB
Nucleocapsid is wrapped in an outer envelope
Between the nucleocapsid and envelope is the matrix protein
The viral envelop is derived from the membrane of the host cell
The viral envelope proteins generally appear as spikes known as peplomers made of glycoproteins
Envelope can help with cell attachment, but also a vaccine target
Helical Capsid Symmetry & Envelope
Influenzavirus
The capsid proteins are aggregated around the viral genome as a flexible hollow tube
The coiled nucleocapsid is wrapped in an envelope to form a virion
Virus With a Complex Symmetry
Smallpox/Poxvirus
The structure is much more complex
Features: an external envelope, complex layer of tubular structure, an internal structure made of a DNA-containing core and lateral bodies
Lateral bodies contain various enzymes essential for virus replication
Viruses with this morphology are among the largest of all viruses
DNA Viruses (6): Naked vs. Enveloped
Hepatitis B: enveloped Herpesviruses: enveloped Poxviruses: enveloped Papovaviruses: naked Parvoviruses: naked Adenoviruses: naked
RNA Viruses (5): Naked vs. Enveloped
Picornaviruses: naked Caliciviruses: naked Arenaviruses: enveloped Orthomyxoviruses: enveloped, segmented genome, 8 ss linear fragments Paramyxoviruses: enveloped
RNA to DNA Viruses
Retroviruses (ssRNA)
Hepadnaviruses (dsDNA)
Segmented Genome
Viral genome: fragmented into two or more nucleic acid molecules; all fragments must be present in order to cause infection
Isocapsidic virus: all fragments of segmented genome located in the same virion like the influenza virus
Heterocapsidic virus: each fragment packaged in a different virion, and successful infection requires that at least one RNA of each type enters host cell
example: alfalfa mosaic virus with 4 different RNA segments
Arboviruses (Arthropod-borne)
Not a family of viruses, just all of them are spread by the bites of mosquitoes, ticks, or sandflies
Bunyaviruses
Flaviviruses
Togaviruses
Enteric viruses
Infect the GI tract; may cause local or systemic infection, with or without GI symptoms; not a family of viruses Adenoviruses Caliciviruses Picornaviruses Rotaviruses
Hepatitis viruses
Infects the liver
Hepatitis A, B, C, D, E, G
not a family, classification by transmission
Sexually Transmitted viruses
Spread by sexual contact; may cause local or systemic infection; not a family
Papillomaviruses
Retroviruses
Herpes
Respiratory viruses
Generally cause upper respiratory tract disease, some infect the lungs; not a family Some adenoviruses Coronaviruses Orthomyxoviruses Paramyxoviruses Rhinoviruses
Poxviridae
Smallpox, vaccinia virus, variola, molluscum contagiosum
linear dsDNA, has polymerase, replication in cytoplasm, enveloped
DNA virus family
Herpesviridae
HSV-1, HSV-2, varicella-zoster (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes viruses 6, 7, and 8
linear dsDNA, does not have its own polymerase, replication and assembly in the nucleus, enveloped with nuclear membrane
DNA virus family
Adenoviridae
Adenovirus
linear dsDNA, does not have its own polymerase, replication in the nucleus, and naked
DNA virus family
Hepadenaviridae
Hepatitis B virus (HBV)
circular ds DNA, has a polymerase, replication in the nucleus via a RNA intermediate, enveloped
DNA virus family
Papoviridae
JC virus, BK virus, SV40, papilloma virus, polyoma
circular dsDNA, does not have its own polymerase, replication in the nucleus, and naked
DNA virus family
Parvoviridae
Parvovirus B19
ssDNA, does not have its own polymerase, replication in the nucleus, and naked
DNA virus family
Paramyxoviridae
Parainfluenza virus, measles, mumps, respiratory syncytial virus (RSV)
RNA virus family
Orthomyxoviridae
Influenza virus types A, B, and C
RNA virus family
Arenaviridae
Lassa fever virus, lymphocytic choriomeningitis virus
RNA virus family
Rhabdoviridae
Rabies virus, vesicular stomatitis virus
RNA virus family
Filoviridae
Ebola virus, Marburg virus
RNA virus family
Bunyaviridae
California encephalitis virus, Hanta virus, hemorrhagic fever virus
RNA virus family
Retroviridae
HIV, human T cell leukemia virus
RNA virus family
Reoviridae
Rotavirus, Colorado tick fever virus
RNA virus family
Picornaviridae
Rhinovirus, poliovirus, echoviruses, coxsackie virus
RNA virus family
Togaviridae
Rubella virus, equine encephalitis viruses (eastern, western, and Venezuelan) Ross River virus
RNA virus family
Flaviviridae
Yellow fever virus, dengue virus, St. Louis encephalitis, Hep C, West Nile
RNA virus family
Caliciviridae
Norwalk virus
RNA virus family
Replication
- Attachment
- Entry (penetration)
- Uncoating
- Macromolecular synthesis: genome replication and protein synthesis
- Assembly
- Budding
- Release via lysis of the host cell
Stages of life of virus- take advantage to make drugs
Best to capture virus at the stage before it enters the cell – Ab specific Ag that we know if present on the surface of the virus then neutralized
Also target receptors on host cells that can be used for the virus; can’t make a drug for CD4 receptor for HIV because the drug will do the same thing as the virus and kill the T cells = bad
Lytic & Lysogenic Cycle
Lytic Pathway:In lysis, the host cell’s membrane is damaged and the cytoplasm is able to leak out. The cell dies rapidly, releasing virus particles
Lysogenic Pathway:The lysogenic path is one of several temperate pathways in which the host cell is not killed outright, but is occupied by the virus and used as a factory for replicating the viral genes.. The viral infection enters a latent period during this process, but eventually undergoes the lytic process
Viral Replication and Drug Targets
Recognition & Attachment are targeted & blocked by antibody and receptor antagonists
Uncoating: Amantadine, Arildone, Rimantadine, Tromantadine
Transcription: Interferon and Antisense oligos
Replication: Nucleoside analogs and Phosphonoformate
Assembly: Protease inhibitors
Steps to Viral Disease
Acquisition (entry into the body): inhalation (most common), skin, sexual transmission, oral-fecal route (GI), hematogenous (blood)
Initiation of infection: viral recognition of receptor/replication and dissemination
Incubation
Prodrome (symptom or set of symptoms that appears shortly before an acute attack of illness; Greek “running ahead of“); pathogenesis with signs and symptoms
Convalescence/recovery
Viral Pathogenesis
Abortive infection (nonproductive infection): the viral infection of a cell in which viral components may be synthesized without the production of infective viruses; infection without causing disease
Lytic infection: infection of a bacterium by a bacteriophage with subsequent production of more phage particles and lysis, or dissolution, of the cell; the viruses responsible are commonly called virulent phages; responsible for acute infections
Persistent infection: chronic (non-lytic, productive), latent, recurrent. transforming (oncogenic); shows signs every now and then
Oncogenic Pathogenesis
Oncogenic viruses can cause
- Transformation causing immortalization of cells
- Uninhibited out-of-control growth
- Loss of contact inhibition causing growth in 3-dimensional mass
- Change in cellular morphology
- Appearance of new surface antigens
Different oncogenic viruses have different means by which they cause transformation:
Providing growth stimulating genes: growth factors
Interfere with tumor suppressor genes: loss of control
Inhibiting cell death by deregulating apoptosis enzymes
Oncogenic Viruses
Epstein-Barr virus: basopharyngeal carcinoma, Burkitt lymphoma (HPV), thymic carcinoma
Hepatitis B virus: primary hepatocellular carcinoma
Hepatitis C virus: primary hepatocellular carcinoma
Human papilloma virus: cervical cancer
Human T cell Leukemia virus: Leukemia/lymphoma
Characteristics of DNA Viruses
DNA viruses have the following characteristics
- Icosahedral symmetry: except pox virus with its complex symmetry
- Double stranded DNA: except parvovirus with ssDNA
- DNA replication in the nucleus: except poxvirus because it replicates in the cytoplasm
DNA Virus Life Cycle
Attachment & penetration by fusion
Latent phase: immediate early protein synthesis
Active replication: early protein synthesis & genome replication
Late Protein synthesis: structural proteins
Assembly and release by exocytosis
Parvoviridae Details
Parvovirus B19: naked, ssDNA, erythema infectiosum/ 5th disease/ slapped cheek fever; mostly in children
Pathogenesis: virus infects immature RBCs (still has nucleus) causing an aplastic crisis in sickle cell patients
Transmission: respiratory aerosols, maternal to fetal
Clinical Syndromes: mild febrile disease, facial rash, lacy body rash, arthritis in adults
Six Pediatric Diseases
1st: rubeola, measles via the measles virus
2nd: scarlet fever via streptococcus pyogenes
3rd: rubella, german measles via rubella virus
4th: staphylococcal scalded skin syndrome via staphylococcus aureus (exfoliative toxin producers)
5th: erythema infectiosum via parvovirus B19
6th: roseola infantum via HHV6-B/HHV7
1,3,5,6 = viral
2,4 = bacterial
Papovaviridae Details
Human papilloma virus: common warts like plantar on the foot sole, painful and flat warts on face and hands in children and young adults, genital warts
Condyloma acuminatum: STD affecting > 20 millions
Laryngeal: young children and adults
Structure: dsDNA, naked
Pathogenesis: enter through breaks in the skinor mucous membranes, 3-4 months to develop Oncogenic potential (E6 binds to p53, E7 binds to Rb)
Epidemiology/transmission: asymptomatic shedding, direct contact, sexual contact, birth, chewing
HPV: More Serious Diseases
Head and neck tumors: serotypes 6 & 11 most common
Anogenital warts
Cervical cancer: serotypes 16 & 18; protective HPV vaccine for young girls
Treatment: spontaneous regression of benign warts possible, cryocautery (liquid nitrogen or dry ice), electrocautery, laser, chemical treatment, interferon, surgical removal
Adenoviridae Details
Adenovirus
Structure: hexahedral with dsDNA, nonenveloped with hexons and penton fibers
Disease pathogenesis: infection of epithelial cells lining the oropharynx, respiratory or GI tract; infections could be lytic, latent or transforming/oncogenic
Transmission: fecal-oral route, fingers, fomites, swimming pools, person to person transmission, crowds such as classrooms and military caserne
Adenovirus Clinical Symptoms
Pharyngitis (with pink eye)- mimics strep throat
Acute respiratory tract disease with fever, cough, pharyngitis, cervical adenitis common among children and military recruits; incubation period is 5-8 days
Other respiratory tract disease: colds, laryngitis, croup, bronchiolitis, pertussis-like syndrome and viral pneumonia
Gastrointestinal disease: diarrhea
Conjunctivitis and epidemic keratoconjunctivitis: swimming pools, shipyard workers, dust and debris
Acute hemorrhagic cystitis: more common in boys
Treatment: none/supportive with cold compresses and topical vasoconstrictors to provide symptomatic relief
Topical antibiotics are rarely necessary, because secondary bacterial infection is uncommon
Vaccine: Oral, live, non-attenuated virus- in the military
Gene therapy: CF, SCID, cancer
Herpesviridae
Herpes simplex virus = Human herpes virus
HHV-1 to HHV-8; large enveloped dsDNA viruses
HSV-1 and HSV-2 are the original herpes simplex viruses
Direct contact- sexual, other intimate
Enter in the mucous membranes or through skin breaks
Virus replicates in cells at base of lesion
Infects the innervating neuron and travels to the ganglion- trigeminal ganglia for HSV-1 and sacral for HSV-2
Virus then returns to the initial site of infection
They are cause of severe pain; cold sores around the face/mouth and genital because they affect the nerves in the tissue = painful
Human Herpesviridae Infections
HHV-1: herpes simplex 1; oral/genital, but predominantly oral/facial
HHV-2: herpes simplex 2; oral/genital, but predominantly genital
HHV-3: Varicella zoster virus (VZV); chicken pox or shingles
HHV-4: Epstein Barr Virus (EBV) or lymphocryptovirus; mononucleosis, Burkitt’s lymphoma, CNS lymphoma in AIDS patients, post-transplant lymphoproliferative syndrome, nasopharyngeal carcinoma
HHV-5: Cytomegalovirus (CMV); mononucleosis like syndrome, retinitis, etc.
HHV-6/7: Roseolovirus; 6th disease
HHV-8: Kaposi’s sarcoma-associated herpes virus/type of rhadinovirus; Kaposi’s sarcoma, primary effusion lymphoma, some types of multicentric Castleman’s disease
HHV-1 and HHV-2
Transmission is via saliva, vaginal secretions, vesicles’ fluid (cold sore)
Both can cause oral and genital lesions
HHV-1: most common, more oral by mouth to skin contact, kissing, sharing drinking glasses, utensils and toothbrushes
HHV-2: STD that affects genitals, anal & perianal, oropharynx
20% of persons 12 years of age or older nationwide are infected with HSV-2
Neonate infection could be lethal
HHV-1 and HHV-2 Clinical Syndromes
Usually benign manifestations, recurrent, clear vesicle, erythematous base
Primary herpes: gingivostomatitis and recurrent as fever blisters
Herpes pharyngitis
Herpetic keratitis
Herpetic whitlow: PAINFUL
Herpes gladiatorum (HG): wrestling
Genital herpes: may be asymptomatic, painful lesions
Herpes encephalitis: mainly HHV-1
Congenital herpes
Recurrence of HHV-1 and HHV-2
HSV stay dormant in the nerve cell body / ganglion:
HSV-1 resides in the trigeminal ganglion
HSV-2 resides in the sacral ganglia
Reactivation occurs from these locations to the respective innervated body areas
This is why: dormant virus from the trigeminal ganglion (oral or facial area) reactivates in the oral or facial region, whereas the dormant virus from the sacral ganglion (lower back/spine area) reactivate to the genital area or the buttock
HHV-1 and HHV-2 Treatment
Herpes drugs are nucleotide analogs, viral DNA polymerase inhibitors, Acyclovir (ACV), Valacyclovir, Penciclovir, Famciclovir
Viral thymidine kinase phosphorylates ACV so cellular enzymes add 2 more PO4 groups to become acyclo-GTP then activated acyclo-GTP incorporates into growing DNA strand and synthesis inhibited
Requirement of viral thymidine kinase for activation makes acyclovir specific, effective, without side effects on the host, useful for prophylaxis
Acyclovir resistance as a result of viral TK mutation causing no ACV activation
Drugs used to treat herpes keratitis and its complicated form dendritic corneal ulcer: Trifluridine, Penciclovir, Acyclovir
HSV Neonatal Infection
Maternal transmission of HSV-2 occurs: during delivery (85% of cases) in uterus, or first few weeks after birth
HSV-2 disease manifestations: skin eye & mouth disease (SEM), CNS disease: encephalitis &/or meningitis, w or w/o SEM, disseminated disease causes death
Varicella Zoster Virus (HHV-3; VZV): Pathogenesis
Viruses replicated in respiratory tract, spread to the blood, then to the lymphatics
After a secondary viremia, the virus spreads to the skin
Dermal manifestations: vesiculopustular rash
Fever
Latent in dorsal root ganglia
Spreads along neural pathways to the skin
Effects single dermatome causing zoster (shingles)
Cause of chicken pox and shingles that affects adults
Anyone who had chicken pox as a child – the virus is still in the body; at old age when there is weak immune system and stressed the virus can become active
Very painful sores on the skin
Epidemiology of VZV
Extremely contagious
Infection exceeding 90% in susceptible households
Spread via respiratory (aerosols) route and contact with skin vesicles
Contagious even before symptoms appear and continues during symptomatic disease
Up to 20% will have reactivation as zoster in old age
Viable virus in zoster, which can be transmitted to children
Varicella
Chickenpox
Fever, maculopapular rash, 14d incubation rash will turn vesicular within hours
Successive crops of lesions 3-5 days
Rash is more severe on trunk, but present on extremities, lesions on scalp, mouth, conjunctivae and vagina
Lesions are itchy so scratching can cause super infection, especially if infected with strep pyogenes, which can cause necrotizing fasciitis
More severe in adults with interstitial pneumonia
Zoster/Shingles: severe pain in the nerve precedes lesions and limited to one dermatome
VZV Treatment
Children: none/supportive
Adults and Immunosuppressed: Acyclovir, Famciclovir, Valcyclovir
Immunosuppressed: immunization with VZV-Ig
VZV vaccine: live, attenuated
Children vaccinated after 12 months of age
